Intestinal Alkaline Phosphatase Prevents Sulfate Reducing Bacteria-Induced Increased Tight Junction Permeability by Inhibiting Snail Pathway

Abstract

Tight junctions (TJs) are essential components of intestinal barrier integrity and protect the epithelium against passive paracellular flux and microbial translocation. Dysfunctional TJ leads to leaky gut, a condition associated with diseases including inflammatory bowel disease (IBD). Sulfate-Reducing Bacteria (SRB) are minor residents of the gut. An increased number of Desulfovibrio, the most predominant SRB, is observed in IBD and other diseases associated with leaky gut. However, it is not known whether Desulfovibrio contributes to leaky gut. We tested the hypothesis that Desulfovibrio vulgaris (DSV) may induce intestinal permeability in vitro. Snail, a transcription factor, disrupts barrier function by affecting TJ proteins such as occludin. Intestinal alkaline phosphatase (IAP), a host defense protein, protects epithelial barrier integrity. We tested whether DSV induced permeability in polarized Caco-2 cells via snail and if this effect was inhibited by IAP. Barrier integrity was assessed by measuring transepithelial electric resistance (TEER) and by 4kDa FITC-Dextran flux to determine paracellular permeability. We found that DSV reduced TEER, increased FITC-flux, upregulated snail protein expression, caused nuclear translocation of snail, and disrupted occludin staining at the junctions. DSV-induced permeability effects were inhibited in cells knocked down for snail. Pre-treatment of cells with IAP inhibited DSV-induced FITC flux and snail expression and DSV-mediated disruption of occludin staining. These data show that DSV, a resident commensal bacterium, can contribute to leaky gut and that snail may serve as a novel therapeutic target to mitigate DSV-induced effects. Taken together, our study suggests a novel underlying mechanism of association of Desulfovibrio bloom with diseases with increased intestinal permeability. Our study also underscores IAP as a novel therapeutic intervention for correcting SRB-induced leaky gut via inhibition of snail.

Protective Properties of Intestinal Alkaline Phosphatase Supplementation on the Intestinal Barrier: Interactions and Effects

“…20 Singh et al emphasizes the use of recIAP as a new therapeutic approach to address leaky gut caused by sulfate-reducing bacteria of snail. 21 Furthermore, supplemented recIAP significantly reduced gut barrier damage, decreased bacterial translocation to the systemic organs, and attenuated systemic inflammation. 22 Overall, bIAP is inexpensive and well-suited for animal or cellular experiments, while the high purity and safety of recIAP have made it more widely used in clinical studies.…”

“…Recent work has shown the importance of recIAP in maintaining gut integrity . Singh et al emphasizes the use of recIAP as a new therapeutic approach to address leaky gut caused by sulfate-reducing bacteria of snail . Furthermore, supplemented recIAP significantly reduced gut barrier damage, decreased bacterial translocation to the systemic organs, and attenuated systemic inflammation .…”

Microbiome–gut–brain dysfunction in prodromal and symptomatic Lewy body diseases

“…Recent work has demonstrated that Desulfovibrio spp. induced intestinal permeability via the snail pathway [126]. Snail is a transcription factor associated with increased intestinal permeability [127][128][129] via negatively regulating tight junctions [130,131].…”

“…Factors resulting from dysbiosis, such as increases in LPS [ 99 – 101 ] and Desulfovibrio spp. [ 126 ] also lead to leaky gut. Recent work has demonstrated that Desulfovibrio spp.…”

Foodborne Carbon Dot Exposure Induces Insulin Resistance through Gut Microbiota Dysbiosis and Damaged Intestinal Mucus Layer

“…The intestinal mucus layer, an essential component of the intestinal barrier, ensures host immune homeostasis by isolating the immune system from gut microbiota. , Some pathogenic bacteria (e.g., Escherichia coli and Desulfovibrio ) have been reported to reduce mucins and tight junction proteins in the intestine, resulting in increased intestinal permeability. − The liver is an important target organ of insulin that plays a dominant role in glucose homeostasis . Notably, the intestines and liver are closely linked by the biliary tract, portal veins, and circulation.…”